High Rate of Passenger Lymphocyte Syndrome after ABO Minor Incompatible Lung Transplantation.

Rationale: Passenger lymphocyte syndrome (PLS) may complicate minor ABO mismatched lung transplantation (LuTX) via donor-derived red cell antibody-induced hemolysis.Objectives: To ascertain the incidence and specificity of PLS-relevant antibodies among the study population as well as the dynamics of hemolysis parameters and the transfusion requirement of patients with or without PLS.Methods: In this cohort study, 1,011 patients who received LuTX between January 2010 and June 2019 were studied retrospectively. Prospectively, 87 LuTX (July 2019 to June 2021) were analyzed. Postoperative ABO antibody and hemolytic marker determinations, transfusion requirement, and duration of postoperative hospital care were analyzed. Retrospectively, blood group A recipients of O grafts with PLS were compared with those without.Measurements and Main Results: PLS affected 18.18% (retrospective) and 30.77% (prospective) of A recipients receiving O grafts, 5.13% of B recipients of O grafts, and 20% of AB patients receiving O transplants. Anti-A and anti-A1 were the predominant PLS-inducing antibodies, followed by anti-B and anti-A,B. Significantly lower hemoglobin values (median, 7.4 vs. 8.3 g/dl; P = 0.0063) and an approximately twice as high percentage of patients requiring blood transfusions were seen in PLS. No significant differences in other laboratory markers, duration of hospital stay, or other complications after LuTX were registered.Conclusions: Minor ABO incompatible LuTX recipients are at considerable risk of developing clinically significant PLS. Post-transplant monitoring combining red cell serology and hemolysis marker determination appears advisable so as not to overlook hemolytic episodes that necessitate antigen-negative transfusion therapy.

Prehospital identification of acute ischaemic stroke with large vessel occlusion: a retrospective study from western Norway.

BACKGROUND: In 2019, the emergency medical services (EMS) covering the western Norway Regional Health Authority area implemented its version of the prehospital clinical criteria G-FAST (Gaze deviation, Facial palsy, Arm weakness, Visual loss, Speech disturbance) to detect acute ischaemic stroke (AIS) with large vessel occlusion (LVO). For patients with gaze deviation and at least one other G-FAST symptom, a primary stroke centre (PSC) may be bypassed and the patient taken directly to a comprehensive stroke centre (CSC) for rapid endovascular treatment (EVT) evaluation. The study aim was to investigate the efficacy of the G-FAST criteria for LVO patient selection and direct transfer to a CSC. METHODS: This retrospective study included patients with code-red emergency medical communication centre (EMCC) stroke suspicion ambulance dispatch between August to December 2020. Stroke suspicion was defined as having at least one G-FAST symptom at EMS arrival. We obtained patient data from dispatches from EMCCs, EMS records and local EVT registries. Clinical features, CT images, and reperfusion treatment were recorded. The test characteristics for gaze deviation plus one other G-FAST symptom in detecting LVO were determined. RESULTS: Among 643 patients, 59 were diagnosed with LVO at hospital arrival. In this group, seven fulfilled the G-FAST criteria for direct transport to a CSC at EMS arrival on scene, resulting in a sensitivity of 12% (95% CI 5% to 23%). The specificity was 99.66% (95% CI 98.77% to 99.96%), the positive predictive value 78%, and the negative predictive value 92%. EVT was performed in 64% (38/59) of LVO cases. Median time from PSC arrival to start of EVT at a CSC was 163 min. CONCLUSION: The use of local G-FAST prehospital criteria by EMS personnel to identify patients with AIS with LVO is not suitable for selection of patients with LVO for direct transfer to a CSC.

Virtual reality simulation training in stroke thrombectomy centers with limited patient volume-Simulator performance and patient outcome.

BACKGROUND: Virtual reality simulation training may improve the technical skills of interventional radiologists when establishing endovascular thrombectomy at limited-volume stroke centers. The aim of this study was to investigate whether the technical thrombectomy performance of interventional radiologists improved after a defined virtual reality simulator training period. As part of the quality surveillance of clinical practice, we also assessed patient outcomes and thrombectomy quality indicators at the participating centers. METHODS: Interventional radiologists and radiology residents from three thrombectomy-capable stroke centers participated in a five months thrombectomy skill-training curriculum on a virtual reality simulator. The simulator automatically registered procedure time, the number of predefined steps that were correctly executed, handling errors, contrast volume, fluoroscopy time, and radiation dose exposure. The design was a before-after study. Two simulated thrombectomy cases were used as pretest and posttest cases, while seven other cases were used for training. Utilizing the Norwegian Stroke Register, we investigated clinical results in thrombectomy during the study period. RESULTS: Nineteen interventional radiologists and radiology residents participated in the study. The improvement between pretest and posttest cases was statistically significant for all outcome measures in both simulated cases, except for the contrast volume used in one case. Clinical patient outcomes in all three centers were well within the recommendations from multi-society consensus guidelines. CONCLUSION: Performance on the virtual reality simulator improved after training. Virtual reality simulation may improve the learning curve for interventional radiologists in limited-volume thrombectomy centers. No correlation alleged, the clinical data indicates that the centers studied performed thrombectomy in accordance with guideline-recommended standards.

Morbidity Milestones Demonstrate Long Disability-Free Survival in Parkinson's Disease Patients with Deep Brain Stimulation of the Subthalamic Nucleus.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD). The long-term benefit in PD patients with STN-DBS in comparison to medical treatment (MT) alone has not yet been demonstrated conclusively. Objectives: To judge the long-term outcome of patients with STN-DBS. Methods: To assess the evolution of PD symptoms and health-related quality of life (HRQoL) after deep brain stimulation (DBS) surgery, we conducted a cross-sectional analysis of 115 patients with STN-DBS with rater-based scales and self-reported questionnaires. In addition, we screened records of all our STN-DBS patients (2001-2019, n = 162 patients) for the onset of the morbidity milestones (falls, hallucinations, dementia, and nursing home placement) to assess disability-free life expectancy. Results: In the first year of STN-DBS, levodopa equivalent dose was reduced and motor function improved. Nonmotor symptoms and cognition remained stable. These effects were similar to previous studies. Morbidity milestones occurred 13 ± 7 years after diagnosis. Motor function, cognition, and HRQoL significantly worsened after the occurrence of any milestone, confirming the clinical relevance of these milestones. After onset of the first milestone, mean survival time was limited to 5 ± 0.8 years, which is comparable with patients with PD but without STN-DBS. Conclusions: On average, PD patients with STN-DBS live with their disease for a longer time, and morbidity milestones occur later in the disease course than in PD patients with MT. As judged by morbidity milestones, morbidity remains compressed into the final 5 years of life in PD patients with STN-DBS.

Biomarkers predictive of atrial fibrillation in patients with cryptogenic stroke. Insights from the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study.

BACKGROUND AND PURPOSE: There are currently no biomarkers to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF. METHODS: Eligible CS and cryptogenic transient ischaemic attack patients underwent 12-month monitoring with ICMs, clinical follow-up and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n = 74) during monitoring and those without AF (n = 185). Receiver operating characteristic curves were created. Biomarkers reaching area under the receiver operating characteristic curve ≥ 0.7 were dichotomized by finding optimal cut-off values and were used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models. RESULTS: B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase, D-dimer and high-sensitivity cardiac troponin I and T were significantly higher in the AF than non-AF group. BNP and NT-proBNP reached the predefined area under the curve level, 0.755 and 0.725 respectively. Optimal cut-off values were 33.5 ng/l for BNP and 87 ng/l for NT-proBNP. Regression analysis showed that NT-proBNP was a predictor of AF in both unadjusted (odds ratio 7.72, 95% confidence interval 3.16-18.87) and age- and sex-adjusted models (odds ratio 4.82, 95% confidence interval 1.79-12.96). CONCLUSION: Several clinically established biomarkers were associated with AF. NT-proBNP performed best as AF predictor and could be used for selecting patients for long-term monitoring with ICMs.

Metric based virtual simulation training for endovascular thrombectomy improves interventional neuroradiologists' simulator performance.

OBJECTIVE: Metric based virtual reality simulation training may enhance the capability of interventional neuroradiologists (INR) to perform endovascular thrombectomy. As pilot for a national simulation study we examined the feasibility and utility of simulated endovascular thrombectomy procedures on a virtual reality (VR) simulator. METHODS: Six INR and four residents participated in the thrombectomy skill training on a VR simulator (Mentice VIST 5G). Two different case-scenarios were defined as benchmark-cases, performed before and after VR simulator training. INR performing endovascular thrombectomy clinically were also asked to fill out a questionnaire analyzing their degree of expectation and general attitude towards VR simulator training. RESULTS: All participants improved in mean total procedure time for both benchmark-cases. Experts showed significant improvements in handling errors (case 2), a reduction in contrast volume used (case 1 and 2), and fluoroscopy time (case 1 and 2). Novices showed a significant improvement in steps finished (case 2), a reduction in fluoroscopy time (case 1), and radiation used (case 1). Both, before and after having performed simulation training the participating INR had a positive attitude towards VR simulation training. CONCLUSION: VR simulation training enhances the capability of INR to perform endovascular thrombectomy on the VR simulator. INR have generally a positive attitude towards VR simulation training. Whether the VR simulation training translates to enhanced clinical performance will be evaluated in the ongoing Norwegian national simulation study.

Recent developments in pre-hospital and in-hospital triage for endovascular stroke treatment.

Triage describes the assignment of resources based on where they can be best used, are most needed, or are most likely to achieve success. Triage is of particular importance in time-critical conditions such as acute ischemic stroke. In this setting, one of the goals of triage is to minimize the delay to endovascular thrombectomy (EVT), without delaying intravenous thrombolysis or other time-critical treatments including patients who cannot benefit from EVT. EVT triage is highly context-specific, and depends on availability of financial resources, staff resources, local infrastructure, and geography. Furthermore, the EVT triage landscape is constantly changing, as EVT indications evolve and new neuroimaging methods, EVT technologies, and adjunctive medical treatments are developed and refined. This review provides an overview of recent developments in EVT triage at both the pre-hospital and in-hospital stages. We discuss pre-hospital large vessel occlusion detection tools, transport paradigms, in-hospital workflows, acute stroke neuroimaging protocols, and angiography suite workflows. The most important factor in EVT triage, however, is teamwork. Irrespective of any new technology, EVT triage will only reach optimal performance if all team members, including paramedics, nurses, technologists, emergency physicians, neurologists, radiologists, neurosurgeons, and anesthesiologists, are involved and engaged. Thus, building sustainable relationships through continuous efforts and hands-on training forms an integral part in ensuring rapid and efficient EVT triage.

Simulation-based team-training in acute stroke: Is it safe to speed up?

BACKGROUND: In acute ischemic stroke (AIS), rapid treatment with intravenous thrombolysis (IVT) is crucial for good clinical outcome. Weekly simulation-based team-training of the stroke treatment team was implemented, resulting in faster treatment times. The aim of this study was to assess whether this time reduction led to a higher proportion of stroke mimics (SMs) among patients who received IVT for presumed AIS, and whether these SM patients were harmed by intracranial hemorrhage (ICH). METHODS: All suspected AIS patients treated with IVT between January 1, 2015 and December 31, 2020 were prospectively registered. In 2017, weekly in situ simulation-based team-training involving the whole stroke treatment team was introduced. To analyze possible unintended effects of simulation training, the proportion of SMs among patients who received IVT for presumed AIS were identified by clinical and radiological evaluation. Additionally, we identified the extent of symptomatic ICH (sICH) in IVT-treated SM patients. RESULTS: From 2015 to 2020, 959 patients were treated with IVT for symptoms of AIS. After introduction of simulation training, the proportion of patients treated with IVT who were later diagnosed as SMs increased significantly (15.9% vs. 24.4%, p = .003). There were no ICH complications in the SM patients treated before, whereas two SM patients suffered from asymptomatic ICH after introduction of simulation training (p = 1.0). When subgrouping SMs into prespecified categories, only the group diagnosed with peripheral vertigo increased significantly (2.5% vs. 8.6%, p < .001). CONCLUSIONS: Simulation training of the acute stroke treatment team was associated with an increase in the proportion of patients treated with IVT for a suspected AIS who were later diagnosed with peripheral vertigo. The proportion of other SM groups among IVT-treated patients did not change significantly. No sICH was detected in IVT-treated SM patients.

Monitoring following acute stroke should be improved. / Overvåkning etter akutt hjerneslag bør bli bedre.

Many serious complications following acute stroke can be prevented and treated. This requires close and systematic monitoring following stroke.

Thrombectomy in large vessel occlusion stroke-Does age matter?

OBJECTIVES: Endovascular treatment (EVT) is the gold standard treatment for emergent large vessel occlusion (LVO). The benefit of EVT for emergent LVO in elderly patients (>80 years old) is still debated as they have been under-represented in randomized controlled trials. Elderly patients with an emergent LVO are a growing population warranting further study. MATERIALS & METHODS: We included 225 consecutive patients treated with EVT for LVO either in the anterior or posterior circulation. The clinical outcome was assessed using the National Institute of Health Stroke Scale (NIHSS). Long-term functional outcome was assessed using 90-day modified ranking scale (mRS). RESULTS: Neurological improvement: A five-year higher age predicted a 0.43 higher mean NIHSS score after EVT (p = .027). After adjusting for confounders (influencing variables), the association between age and post-interventional NIHSS was reduced and non-significant (p = .17). At discharge, a five-year higher age predicted a 0.74 higher mean NIHSS (p = .003). After adjusting for confounders this association was reduced and non-significant (p = .06). Long-term functional outcome: A five-year higher age predicted a 0.20 higher mRS at three months (p < .001). When adjusting for confounders this number was reduced to 0.16, yet still highly significant (p < .001). CONCLUSIONS: Age seems to have a minor role in predicting neurological improvement after EVT but has an impact on long-term functional outcome. The decision to perform or withhold EVT should therefore not solely be based on age.

Cost-effectiveness of a quality improvement project, including simulation-based training, on reducing door-to-needle times in stroke thrombolysis.

BACKGROUND: Rapid revascularisation in acute ischaemic stroke is crucial to reduce its total burden including societal costs. A quality improvement (QI) project that included streamlining the stroke care pathway and simulation-based training was followed by a significant reduction in median door-to-needle time (27 to 13 min) and improved patient outcomes after stroke thrombolysis at our centre. Here, we present a retrospective cost-effectiveness analysis of the QI project. METHODS: Costs for implementing and sustaining QI were assessed using recognised frameworks for economic evaluations. Effectiveness was calculated from previously published outcome measures. Cost-effectiveness was presented as incremental cost-effectiveness ratios including costs per minute door-to-needle time reduction per patient, and costs per averted death in the 13-month post-intervention period. We also estimated incremental cost-effectiveness ratios for a projected 5-year post-intervention period and for varying numbers of patients treated with thrombolysis. Furthermore, we performed a sensitivity analysis including and excluding costs of unpaid time. RESULTS: All costs including fixed costs for implementing the QI project totalled US$44 802, while monthly costs were US$2141. We calculated a mean reduction in door-to-needle time of 13.1 min per patient and 6.36 annual averted deaths. Across different scenarios, the estimated costs per minute reduction in door-to-needle time per patient ranged from US$13 to US$29, and the estimated costs per averted death ranged from US$4679 to US$10 543. CONCLUSIONS: We have shown that a QI project aiming to improve stroke thrombolysis treatment at our centre can be implemented and sustained at a relatively low cost with increasing cost-effectiveness over time. Our work builds on the emerging theory and practice for economic evaluations in QI projects and simulation-based training. The presented cost-effectiveness data might help guide healthcare leaders planning similar interventions.

Machine Learning Algorithms Versus Thresholding to Segment Ischemic Regions in Patients With Acute Ischemic Stroke.

OBJECTIVE: Computed tomography (CT) scan is a fast and widely used modality for early assessment in patients with symptoms of a cerebral ischemic stroke. CT perfusion (CTP) is often added to the protocol and is used by radiologists for assessing the severity of the stroke. Standard parametric maps are calculated from the CTP datasets. Based on parametric value combinations, ischemic regions are separated into presumed infarct core (irreversibly damaged tissue) and penumbra (tissue-at-risk). Different thresholding approaches have been suggested to segment the parametric maps into these areas. The purpose of this study is to compare fully-automated methods based on machine learning and thresholding approaches to segment the hypoperfused regions in patients with ischemic stroke. METHODS: We test two different architectures with three mainstream machine learning algorithms. We use parametric maps as input features, and manual annotations made by two expert neuroradiologists as ground truth. RESULTS: The best results are produced with random forest (RF) and Single-Step approach; we achieve an average Dice coefficient of 0.68 and 0.26, respectively for penumbra and core, for the three groups analysed. We also achieve an average in volume difference of 25.1 ml for penumbra and 7.8 ml for core. CONCLUSIONS: Our best RF-based method outperforms the classical thresholding approaches, to segment both the ischemic regions in a group of patients regardless of the severity of vessel occlusion. SIGNIFICANCE: A correct visualization of the ischemic regions will guide treatment decisions better.

Time-Based Decision Making for Reperfusion in Acute Ischemic Stroke.

Decision making in the extended time windows for acute ischemic stroke can be a complex and time-consuming process. The process of making the clinical decision to treat has been compounded by the availability of different imaging modalities. In the setting of acute ischemic stroke, time is of the essence and chances of a good outcome diminish by each passing minute. Navigating the plethora of advanced imaging modalities means that treatment in some cases can be inefficaciously delayed. Time delays and individually based non-programmed decision making can prove challenging for clinicians. Visual aids can assist such decision making aimed at simplifying the use of advanced imaging. Flow charts are one such visual tool that can expedite treatment in this setting. A systematic review of existing literature around imaging modalities based on site of occlusion and time from onset can be used to aid decision making; a more program-based thought process. The use of an acute reperfusion flow chart helping navigate the myriad of imaging modalities can aid the effective treatment of patients.

Brain monitoring in hospitals needs to be strengthened. / Hjerneovervåking i sykehusene må styrkes.

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

Outcome of lung transplantation in cystic fibrosis patients with severe asymmetric chest cavities.

Objective: A small but relevant proportion of patients with cystic fibrosis develop severely asymmetric chest cavities during the course of their disease. For these patients, the best surgical approach for lung transplantation (LTx) and optimal size matching strategies are controversial. Methods: All cystic fibrosis patients with asymmetric chest cavities who underwent LTx at the Medical University of Vienna between 2003 and 2017 were identified (n = 13). Patients were grouped according to different surgical strategies: unilateral full-size and contralateral lobar transplantation (n = 4), standard double LTx after mobilization/repositioning of the mediastinum (n = 3), oversized single LTx followed by pneumonectomy on the smaller contralateral side (n = 4), and single LTx after a remote contralateral pneumonectomy (n = 2). Results: Compared with cystic fibrosis patients with symmetric chests (n = 276, control group), the perioperative management of patients with asymmetric chests was often more complicated. Consequently, 90-day mortality was heightened (23.1% vs 6.5%). Despite this, long-term survival was good with a 5-year survival rate of 69% compared with 78%. Of note, outcome seemed superior for patients who surgery was undertaken with a bilateral compared with a unilateral approach. Conclusions: Severely asymmetric chest cavities present challenges in regard to the surgical strategy, size matching, and postoperative management. However, in carefully selected patients, LTx provides an adequate long-term outcome.

Clinical outcomes and safety profile of Tenecteplase in wake-up stroke.

BACKGROUND: Tenecteplase has probably pharmacological and clinical advantages in the treatment of acute ischemic stroke. There are lacking data about safety and efficacy of tenecteplase in wake-up stroke (WUPS). AIMS: To investigate safety and efficacy of tenecteplase compared to alteplase in WUPS patients included in NOR-TEST. METHODS: WUPS patients in NOR-TEST were included in the study based on DWI-FLAIR mismatch. Included patients randomly assigned (1:1) to receive intravenous tenecteplase 0.4 mg/kg (to a maximum of 40 mg) or alteplase 0.9 mg/kg (to a maximum of 90 mg). Neurological improvement was defined as 1) favorable functional outcome at 90 days modified Rankin Scale (mRS) of 0 or 1 and 2) neurological improvement measured with the National Institutes of Health Stroke Scale (NIHSS) of 4 points within 24 hours as compared to admission NIHSS or NIHSS 0 at 24 hours. RESULTS: Of 1100 patients from 13 stroke centers included in NOR-TEST, 45 were WUPS patients. Of these, 5 patients were stroke mimics and excluded. Of the remaining 40 patients (3.6%), 24 were treated with alteplase (60%). There was no difference in the number of patients achieving a good clinical outcome (mRS 0-1) in either treatment group. Patients treated with tenecteplase showed a better early neurological improvement (87.5% vs 54.2%, P = 0.027). No ICH was detected on MRI/CT 24-28 hours after thrombolysis. CONCLUSIONS: In WUPS patients treated in NOR-TEST, there was no difference in clinical outcomes at 90 days and no ICH events or deaths were observed in either alteplase- or tenecteplase-treated patients. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01949948.

Improving Stroke Care in Times of the COVID-19 Pandemic Through Simulation: Practice Your Protocols!

During the coronavirus disease 2019 (COVID-19) pandemic, infectious disease control is of utmost importance in acute stroke treatment. This is a new situation for most stroke teams that often leads to uncertainty among physicians, nurses, and technicians who are in immediate contact with patients. The situation is made even more complicated by numerous new regulations and protocols that are released in rapid succession. Herein, we are describing our experience with simulation training for COVID-19 stroke treatment protocols. One week of simulation training allowed us to identify numerous latent safety threats and to adjust our institution-specific protocols to mitigate them. It also helped our physicians and nurses to practice relevant tasks and behavioral patterns (eg, proper donning and doffing PPE, where to dispose potentially contaminated equipment) to minimize their infectious exposure and to adapt to the new situation. We therefore strongly encourage other hospitals to adopt simulation training to prepare their medical teams for code strokes during the COVID-19 pandemic.